Safety and Efficacy of Low-Dose Eptifibatide for Tandem Occlusions in Acute Ischemic Stroke.

OBJECTIVES: The optimal treatment strategy for ischemic stroke in patients presenting with tandem occlusions of the internal carotid artery remains controversial. Several studies have demonstrated better clinical outcomes after eptifibatide, which is a short half-life antiplatelet agent. This retrospective analysis focused on the safety and efficacy of low-dose eptifibatide administration in stroke patients with tandem lesions. METHODS: We evaluated the results of endovascular treatment in 148 stroke patients with tandem lesions. Patients in whom balloon angioplasty alone resulted in satisfactory cerebral flow did not receive eptifibatide (33 patients); others received this drug together with stent implantation (115 patients). Eptifibatide was given as an intravenous bolus of 180 µg/kg and then in a modified low dose of 1 µg/kg/min for 24 hours. RESULTS: There were no statistically significant differences between both groups regarding 30-day mortality, frequency of thrombotic events, or hemorrhagic complications. An analysis of clinical status at 30-day follow-up revealed that the administration of eptifibatide was associated with a statistically significant better outcome: a higher rate of either no neurological symptoms or only mild symptoms (4 NIHSS points maximally). CONCLUSIONS: The administration of eptifibatide in stroke patients presenting with tandem lesions is relatively safe. Moreover, treatment with this drug can improve clinical outcomes in these challenging patients.

Results of Numerical Modeling of Blood Flow in the Internal Jugular Vein Exhibiting Different Types of Strictures.

The clinical relevance of nozzle-like strictures in upper parts of the internal jugular veins remains unclear. This study was aimed at understanding flow disturbances caused by such stenoses. Computational fluid dynamics software, COMSOL Multiphysics, was used. Two-dimensional computational domain involved stenosis at the beginning of modeled veins, and a flexible valve downstream. The material of the venous valve was considered to be hyperelastic. In the vein models with symmetric 2-leaflets valve without upstream stenosis or with minor 30% stenosis, the flow was undisturbed. In the case of major 60% and 75% upstream stenosis, centerline velocity was positioned asymmetrically, and areas of reverse flow and flow separation developed. In the 2-leaflet models with major stenosis, vortices evoking flow asymmetry were present for the entire course of the model, while the valve leaflets were distorted by asymmetric flow. Our computational fluid dynamics modeling suggests that an impaired outflow from the brain through the internal jugular veins is likely to be primarily caused by pathological strictures in their upper parts. In addition, the jugular valve pathology can be exacerbated by strictures located in the upper segments of these veins.

Adenoviral vector-based COVID-19 vaccines-associated cerebral venous sinus thromboses: Are those adverse events related to the formation of neutrophil extracellular traps?

In March and April 2021 several countries temporarily suspended vaccinations with adenoviral vector-based COVID-19 vaccines. Concerns of national regulators particularly regarded very rare cases of cerebral venous sinus thrombosis after immunization with this type of vaccine. Until now, these adverse events were interpreted as standard hypercoagulable events, but their clinical characteristics suggest that they may actually represent unique thrombotic disorders referred to as immunothrombosis. In this paper it is speculated that it is possible that immunothrombosis after this type of vaccine results from formation of neutrophil extracellular traps (NETs) in veins affected by stagnant blood flow. Such a stasis occurs in individuals with anatomical variants of cerebral venous outflow, which may explain why these events are primarily seen in the cerebral veins. It has already been found that SARS-CoV-2 spike protein can evoke release of NETs. There is also a question if thrombotic events after adenoviral vector-based COVID-19 vaccines could be avoided. These vaccines will still be needed to curb COVID-19 worldwide, since they do not require transportation and storage at very low temperatures. Perhaps, vaccinations with these vaccines should be performed in combination with prophylactic administration of dipyridamole, which is an inexpensive pharmaceutical agent reducing the release of NETs.

En marzo y abril de 2021 diversos países suspendieron temporalmente la vacunación con vacunas frente a COVID-19 basadas en vectores adenovirales. Las preocupaciones de los reguladores nacionales contemplaban en particular los casos raros de trombosis del seno venoso cerebral tras la inmunización con este tipo de vacunas. Hasta la fecha dichos episodios han sido interpretados como eventos estándar de hipercoagulación, aunque sus características clínicas sugieren que realmente pueden representar trastornos trombóticos únicos denominados inmunotrombosis. En este documento se especula la posibilidad de que la inmunotrombosis tras la administración de este tipo de vacuna se derive de la formación de trampas extracelulares de neutrófilos (NETs) en las venas afectadas por un flujo sanguíneo estancado. Dicha estasis se produce en individuos con variantes anatómicas de flujo venoso cerebral saliente, lo cual puede explicar por qué estos episodios se aprecian primeramente en las venas cerebrales. Se ha comprobado que la proteína pico de SARS-CoV-2 puede evocar la liberación de NETs. También está la cuestión de si pueden evitarse los episodios trombóticos tras la administración de las vacunas frente a COVID-19 basadas en vectores adenovirales. Dichas vacunas seguirán siendo necesarias si queremos doblegar la COVID-19 a nivel mundial, ya que no requieren transporte ni almacenamiento a muy bajas temperaturas. Quizás la vacunación con estas vacunas debería realizarse en combinación con la administración profiláctica de dipiridamol, que es un agente farmacéutico económico que reduce la liberación de NETs.

Is digital necrosis in COVID-19 caused by neutrophil extracellular traps: Potential therapeutic strategies.

Some of the COVID-19 patients present with ischemic lesions of their finger and toes. Standard anticoagulant therapy is usually unsuccessful for the treatment of this unique presentation of COVID-19. In this review current evidence is presented, which supports the hypothesis that these necrotic lesions are primarily related to the formation of neutrophil extracellular traps is blood vessels. Also, currently available and potential pharmacological methods of the management of this unique thrombotic complication are discussed. Drugs that possibly could be used in COVID-19 patients suffering from acute ischemia of distal parts of the extremities particularly comprise DNase I and DNase1L3, which could directly dissolve these extracellular webs that are mostly composed of DNA. However, at the moment, none of these enzymes are registered for an intravascular administration in humans. Lactoferrin and dipyridamole are other pharmaceutical agents that could potentially be used for the treatment of neutrophil extracellular traps-evoked digital ischemia. These agents exhibit prophylactic activity against excessive formation of these extracellular structures. Such an experimental treatment should probably be accompanied by standard antithrombotic management with heparin. Open-label and then randomized trials are needed to confirm feasibility, safety and efficacy of the above-suggested management of critically ill COVID-19 patients.

Mid-term and late results of endovascular treatment for symptomatic carotid artery stenosis under proximal protection.

INTRODUCTION: Although filters are still preferred during carotid stenting, proximal protection systems (PPS) are increasingly used during these procedures. PPS seem to be safer than distal systems, especially in symptomatic patients, but evidence supporting their use is limited. AIM: This was a post hoc survey with 30-day mid-term and long-term follow up, which was aimed at assessment of the safety and efficacy of stenting of the internal carotid artery under PPS in symptomatic patients. MATERIAL AND METHODS: We analysed the results of stenting in 120 symptomatic patients presenting with at least 60% stenosis. Patients were aged 67.9 ±9.8 years, and 12 patients were older than 80 years. An occlusion of contralateral artery was found in 5 patients and bilateral stenosis in 26 patients. The primary endpoint of this study was the proportion of patients who had new neurological events, including transient ischemic attack and minor or major stroke in 30-day follow-up. The secondary endpoint was a composite of technical and clinical success. During long-term follow-up we assessed new neurological events and stenoses of implanted stents. RESULTS: The incidence of new neurological events during 30-day follow-up was 0.8%. The rate of technical success defined by secondary endpoint was 100%. Mean internal carotid artery stenosis before and after stent implantation was 93.8 ±9% and 8.4 ±6.3%, respectively (p < 0.001). Procedural success was achieved in all cases. During long-term follow-up there were two (1.7%) asymptomatic in-stent stenoses and no (0%) new neurological events. CONCLUSIONS: Endovascular management of symptomatic carotid stenosis under PPS is safe, feasible, and appears to be a good alternative to surgical endarterectomy.

Numerical modeling of blood flow in the internal jugular vein with the use of computational fluid mechanics software.

OBJECTIVES: To determine the site and nature of altered hemodynamics in pathological internal jugular veins. METHOD: With the use of computational fluid mechanics software we simulated blood flow in 3 D models of the internal jugular veins that exhibited different morphologies, including nozzle-like strictures in their upper parts and valves in the lower parts. RESULTS: In a majority of models with nozzle-like strictures, especially those positioned asymmetrically, abnormal flow pattern was revealed, with significant flow separation and regions with reversed flow. Abnormal valves had no significant impact on flow in a case of already altered flow evoked by stricture in upper part of the vein. CONCLUSIONS: In our jugular model, cranially-located stenoses, which in clinical practice are primarily caused by external compression, cause more significant outflow impact respect to endoluminal defects and pathological valves located more caudally.

The effect of the calibre and length of needle on the stability of sclerosing foam.

OBJECTIVES: Little is known how calibre and length of needles affect the stability of sclerosing foam. METHODS: Foams were made of 0.5%, 1%, 2% and 3% polidocanol, and 0.2%, 0.5%, 1% and 3% sodium tetradecyl sulfate (STS), which were mixed with air in the proportion of 4:1. These foams were ejected through needles with the length of: 4 mm, 6 mm and 13 mm, and diameter of: 0.26 mm, 0.3 mm and 0.4 mm. RESULTS: Foams made of more concentrated polidocanol were more stable. Regarding STS an opposite relationship was revealed. Foams made of polidocanol were more stable if ejected through a longer needle, while the length of needle did not significantly affect stability of STS foams. Foams ejected through 0.26 mm diameter needles were very unstable. In the case of 0.5% polidocanol, 0.3x6mm needle provided atypically stable foam. CONCLUSION: In order to inject maximally stable foam, calibre and length of needle should be taken into account.

Blood flow in the internal jugular veins during the spaceflight - Is it actually bidirectional?

Recently intriguing results of the research performed on astronauts of the International Space Station have been published. Unexpectedly, in some crew members a stagnant and bidirectional flow in the internal jugular vein was found, and in one of the astronauts this vein seemed to be totally thrombosed. If it actually were the case that in the settings of weightlessness there is a substantial risk of jugular vein thrombosis, any long-term human space missions would be extremely dangerous. Yet, we interpret these findings differently. In our opinion, what has been explained as bidirectional flow, actually represented the flow separation, and what has been described as occluded vein was rather the vein with recirculating and low-velocity flow. In this paper, basing on physical laws governing the flow of fluids, we describe how the flow separation and recirculation can develop in a dilated internal jugular vein, how it can affect cerebral outflow through this vein, why such a phenomenon is more likely in the settings of microgravity and how future research on this topic should be directed.

Potential Involvement of Impaired Venous Outflow from the Brain in Neurodegeneration: Lessons Learned from the Research on Chronic Cerebrospinal Venous Insufficiency.

About 10 years ago, the so-called chronic cerebrospinal venous insufficiency syndrome was discovered. This clinical entity, which is associated with extracranial venous abnormalities that impair venous outflow from the brain, was initially found exclusively in multiple sclerosis patients. Currently, we know that such venous lesions can also be revealed in other neurological pathologies, including Alzheimer's and Parkinson's diseases. Although direct causative role of chronic cerebrospinal venous insufficiency in these neurological diseases still remains elusive, in this paper, we suggest that perhaps an abnormal venous drainage of the brain affects functioning of the glymphatic system, which in turn results in the accumulation of pathological proteins in the cerebral tissue (such as ß-synuclein, ß-amyloid and α-synuclein) and triggers the venous outflow from the cranial cavity and circulation of the cerebrospinal fluid in the settings of neurodegenerative disease.

Endovascular management of carotid and vertebral artery dissections with new generation double-mesh stent and protection systems - single-center early and midterm results.

INTRODUCTION: Symptomatic dissections (SD) of cervical arteries are still a therapeutic problem. Although endovascular management (EM) is currently a preferred method of treatment of SD, complications associated with this method of treatment in published reports are quite frequent (3-16%). AIM: In this retrospective study we analyzed the results of EM with novel, double-mesh stent and protection systems (PS) for SD of the internal carotid (IC) or vertebral arteries (VA) that coexisted with hemodynamically significant stenosis or aneurysmatic dilatation of the dissected artery. MATERIAL AND METHODS: We evaluated the results of EM in 19 patients (men 15, median age: 55, range: 25-83), presenting with SD of the IC or VA with coexisting stenosis and/or aneurysmatic dilatation of the artery in segments C1-C5 of IC or V0-V4 of VA. Twelve patients had a stroke, 6 TIA, and 3 patients a headache and/or a neck pain with Horner syndrome. Stents and PS were tailored according to the location, length of dissection and coexisting stenotic or aneurysmatic lesions. RESULTS: There were no new strokes, in-hospital deaths or other serious morbidities during the procedure and postprocedural hospital stay. There were no fatalities during 6-40 months of follow-up. In control angiographies performed after interventions all patients demonstrated a patent target artery, complete coverage of the dissection and aneurysm by stents and no new lesions in the area of the previous dissection. CONCLUSIONS: The results of this study indicate that EM of SD of IC and VA with the new stents and PS is safe and effective with good early and midterm results.

Mechanical rotational thrombectomy with Rotarex system augmented with drug-eluting balloon angioplasty versus stenting for the treatment of acute thrombotic and critical limb ischaemia in the femoropopliteal segment.

INTRODUCTION: Mechanical thrombectomy is an alternative to local thrombolysis for the treatment of severe ischaemia in the femoropopliteal segment, but stent implantation is usually required after this procedure. The use of drug-eluting balloons (DEBs) may overcome long-term problems associated with stents, but it remains unclear how often such a treatment is technically feasible and efficient. AIM: This post hoc single-centre study was aimed at assessment of the feasibility, safety and efficacy of mechanical thrombectomy followed by application of DEBs. MATERIAL AND METHODS: Fifty-one patients, aged 69.1 ±11.6 years, were managed for acute thrombotic or chronic critical ischaemia in the femoropopliteal segment using the Rotarex device. Following mechanical thrombectomy, on condition that there was no significant residual stenosis or dissection, lesions were managed with paclitaxel-coated DEBs, which was a desired strategy (24 patients). The remaining 25 patients underwent stent implantations, which was regarded as bailout treatment. Final follow-up was scheduled 12 months after the procedure. RESULTS: The primary-assisted patency rate after mechanical rotational thrombectomy with additional balloon angioplasty and/or stenting was 97.1% (49 patients). The early mortality rate was 2.0% (1 patient) and the amputation rate was 4.1% (2 patients). There were no late mortalities or limb amputations at 12-month follow-up, but significant restenoses occurred in 13 (27.1%) patients. These restenoses were more frequent in patients who underwent stent implantation (45.5%) than those managed with DEBs (12.5%), and in patients managed for secondary lesions. CONCLUSIONS: In selected patients mechanical rotational thrombectomy in the femoropopliteal segment followed by application of DEB is a safe, effective and long-lasting method of revascularisation.

Possible Role of Glymphatic System of the Brain in the Pathogenesis of High-Altitude Cerebral Edema.

In this article, we suggest that the glymphatic system of the brain can play an important role in the pathogenesis of high-altitude cerebral edema (HACE). Water enters the intercellular space of the brain primarily through aquaporin-4 (AQP-4) water channels, the main component of the glymphatic system, whereas acetazolamide, pharmacological agent used in the prevention of HACE, is the blocker of the AQP-4 molecule. In animal experiments, cerebral edema caused by hypobaric hypoxia was associated with an increased expression of AQP-4 by astrocytes. Also, the glymphatic system is primarily active during sleep, although sleep at high altitude is a well-known risk factor of developing HACE. All these findings support our hypothesis. We suggest that future research on the prevention and treatment of HACE should involve factors that are already known to modify activity of the glymphatic system, such as angiotensin-converting enzyme inhibitors or other pharmaceutical agents affecting noradrenergic system of the brain, body posture during sleep, anatomy of the veins draining the cranial cavity, and the influence of physical activity before and during exposure to high altitude, especially in relation to sleep.